Method of enhancing drug uptake from a drug-eluting balloon

ABSTRACT

An intravascular device can comprise a carrier and an expansion apparatus. The device can be used for intravascular treatment of atherosclerotic plaque. The carrier can be reversibly expandable and collapsible within a vessel and can have ribbon strips extending between opposite ends in a longitudinal direction of the carrier. The ribbon strips can each be formed with a plurality of elongated protrusions thereon. The expansion apparatus can be used to actuate the ribbon strips each with the plurality elongated protrusions to pierce a luminal surface of the plaque with lines or patterns of microperforations which act as serrations for forming cleavage lines or planes in the plaque.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a continuation of U.S. application Ser. No.13/689,657 filed on Nov. 29, 2012, which is a continuation of U.S.application Ser. No. 12/408,035, filed Mar. 20, 2009, now U.S. Pat. No.8,323,243, which claims the benefit of priority to U.S. ProvisionalApplication 61/038,477, filed Mar. 21, 2008. All of above applicationsare hereby incorporated by reference herein in their entirety and are tobe considered part of this application.

FIELD OF THE INVENTION

The present invention is directed to a device and method for openingblood vessels in the body occluded by atherosclerotic plaque bypre-angioplasty serration and dilatation of the plaque.

BACKGROUND OF THE INVENTION

Atherosclerotic occlusive disease is the primary cause of stroke, heartattack, limb loss, and death in the US and the industrialized world.Atherosclerotic plaque farms a hard layer along the wall of an arteryand is comprised of calcium, cholesterol, compacted thrombus andcellular debris. As the atherosclerotic disease progresses, the bloodsupply intended to pass through a specific blood vessel is diminished oreven prevented by the occlusive process. One of the most widely utilizedmethods of treating clinically significant atherosclerotic plaque isballoon angioplasty.

Balloon angioplasty is an accepted and common method of opening blockedor narrowed blood vessels in every vascular bed in the body. Balloonangioplasty is performed with a balloon angioplasty catheter. Theballoon angioplasty catheter consists of a cigar shaped, cylindricalballoon attached to a catheter. The balloon angioplasty catheter isplaced into the artery from a remote access site that is created eitherpercutaneously or through open exposure of the artery. The catheter 1 ispassed along the inside of the blood vessel over a wire that guides theway of the catheter. The portion of the catheter with the balloonattached is placed at the location of the atherosclerotic plaque thatrequires treatment. The balloon is inflated to a size that is consistentwith the original diameter of the artery prior to developing occlusivedisease.

When the balloon is inflated, the plaque is stretched, compressed,fractured, or broken, depending on its composition, location, and theamount of pressure exerted by the balloon. The plaque is heterogeneousand may be soft in some areas or hard in others causing unpredictablecleavage planes to form under standard balloon angioplasty. The basicmechanism of balloon angioplasty relies to on a combination of actionscaused by the balloon exerting pressure on the atherosclerotic plaque,including; compression of the plaque and the fracture of the hard,circumferentially calcified portion of the plaque. Balloon angioplastycauses plaque disruption and sometimes it causes arterial injury at theangioplasty site. Balloon angioplasty is often performed at highinflation pressures, in excess of 4 atmospheres, very commonly at 8 atmand sometimes up to 22 atm. Therefore, the results of balloonangioplasty are unpredictable.

When the angioplasty balloon is expanded with enough pressure to open ahard plaque dissection often occurs; the hardened areas become disruptedand partially separated from the arterial wall and are prone to liftingup as flaps or chunks. The higher the pressure of balloon angioplastyand the more rapidly the pressure reaches a high level, the more oftenit produces dissection. The random cleavage planes that are created bythe dissection depend upon the composition of the plaque and thepressure exerted upon it. The cleavage planes tend to be wandering,longitudinal lines. The depth of the cleavage planes or fractures thatare created by balloon angioplasty varies significantly and may besuperficial or may be deep and extend all the way to the media of thearterial wall. To the extent that the cleavage plane goes across theline of flow, that is perpendicular or diagonal to the axial directionof the vessel, there is the potential for partial or complete lifting ofa flap. When a flap of fractured plaque has lifted, it may cause acuteocclusion or blockage of blood flow, or leave a significant residualstenosis, or may extend to create a larger flap.

Frequently, a segment of the plaque is more resistant to dilatation thanthe remainder of the plaque. When this occurs, greater pressure pumpedinto the balloon results in full dilatation of the balloon to itsintended size. The balloon is deflated and removed and the arterysegment is reexamined, usually using angiography. The process of balloonangioplasty is one of uncontrolled plaque disruption. The lumen of theblood vessel at the site of treatment is usually somewhat larger, butnot always and not reliably. Some of the cleavage planes created byfracture of the plaque with balloon angioplasty form dissection. Adissection occurs when a portion of the plaque is lifted away from theartery and is not fully adherent and may be mobile or loose. The plaquethat has been disrupted by dissection protrudes into the flowstream. Ifthe plaque lifts completely in the direction of blood flow, it mayimpede flow or cause acute occlusion of the blood vessel.

The dissection of plaque after balloon angioplasty is treated to preventocclusion and to resolve residual stenosis. A common practice has beento place a retaining structure, such as a rigid or semi-rigid tubularstent, to hold the artery open after angioplasty and retain thedissected plaque material back against the wall of the blood vessel tokeep an adequate lumen open for blood flow. The clinical management ofdissection or residual narrowing after balloon angioplasty is currentlyaddressed through the development of increasingly complex stentstructures. However, there has been substantial clinical evidence ofdisadvantages with using stents, including body rejection of a largemass of foreign material, and the emplacement of extensive surface areaof a stent that may become sites for re-accumulation of plaquere-stenosis due to smooth muscle cell growth and intimal hyperplasia.

In juxtaposition to lesions that may develop significant dissectionafter balloon angioplasty, a substantial proportion of patients do notsustain major dissections as a result of balloon angioplasty. This seemsto depend on several factors, including; the location and morphology ofthe lesion, and the pressure required to dilate the lesion duringballoon angioplasty, but is also to some extent unpredictable. Thissituation does not require a stent. When post-angioplasty blood vesselsshow no sign or minimal sign of dissection and are left to heal on theirown, i.e., when no stent is implanted, especially in the iliac andfemoro-popliteal arteries, the rate of acute re-occlusion is low.

The long-term success of balloon angioplasty alone in many cases mayproduce the same or better long-term results than if a stent wasemplaced. Balloon angioplasty without stenting therefore remains one ofthe most common endovascular procedures and one of the most costeffective.

When it is deemed necessary that a stent is required at a given site ofplaque buildup, it is highly desirable to have the ability to fullydilate the stent within the lesion. This is a problem that has been thefocus of intensive investigation and is due to the fact that somelesions are so recalcitrant to dilatation, that they cannot be dilatedeven at very high pressures.

Accordingly, it is deemed highly desirable to dilate plaque material soas to create a smooth post-angioplasty surface without elevated flaps ordissection, and to reduce the need for post-angioplasty stent placement.It is further desirable to provide a method of dilatation that permitsbetter expansion of the lumen, such that if a stent is required, itallows the stent to be fully opened. In cases where local sites ofpost-angioplasty dissections or non-smooth lumen walls presentthemselves, it may be desirable to implant a retaining structure otherthan a stent which offers a minimal surface footprint and exerts lowlateral pressures against the post-angioplasty surface.

SUMMARY OF THE INVENTION

To overcome the problems and disadvantages of prior practices ofdilating plaque material in blood vessels through balloon angioplastyand with or without the use of post-angioplasty stent emplacement, thepresent invention employs an intravascular device carrying rows orpatterns of small sharp spikes that are actuated by an expansion balloonor other apparatus to pierce the luminal surface of atheroscleroticplaque with lines or patterns of microperforations which act asserrations for forming cleavage lines, expansion lines, or planes in theplaque.

With the microperforation and serration procedure, the plaque can becompressed and the artery lumen safely and accurately dilated andstretched during balloon angioplasty to its intended diameter withoutcreating numerous and substantial dissections and elevated flaps. Themicroperforation and serration enable the plaque to be dilated moreevenly and smoothly and avoid forming random cracks that may lead todissection and residual stenosis. The plaque, after it has beenpre-treated with microperforation and serration, may also be dilatedwith lower pressure than that which is used in standard balloonangioplasty. The lower intra-balloon pressure (e.g., less than or equalto 4 atm and very often less than or equal to 2 atm) causes lessdisruption of the plaque, fewer dissections, and less injury to theartery wall. This “low pressure” or “minimal injury” angioplasty is lesslikely to cause the biological reaction that often follows balloonangioplasty with neointimal hyperplasia or smooth muscle cellreplication.

In addition, microperforation and serration permits the plaque to expandwith less fracturing or disruption of the plaque during balloonangioplasty. This decreases the need for stent placement to be used totreat dissection or residual stenosis after balloon angioplasty. Ifextensive dissections and non-smooth luminal wall surfaces require astent to be placed, the improved dilatation of the lumen obtained withpre-angioplasty perforation and serration would allow a stent to be morefully opened.

In cases where one or more local sites of plaque dissections or flapspresent themselves, a thin, ring-shaped tack device may be placed atonly the location of each specific problem site, so that the amount offoreign material emplaced as a retaining structure in the blood vesselcan be minimized and exert only low lateral pressures against thepost-angioplasty surface. A novel method and device for applying aring-shaped tack device as a retaining structure for plaque in the bloodvessel is described in U.S. patent application Ser. No. 11/955,331,filed Dec. 12, 2007, entitled “Device for Tacking Plaque to Blood VesselWall”, which is incorporated by reference herein.

Preferred embodiments of the perforation and serration device includethree varying methods for spike deployment, through mechanical, balloon,and balloon-assist deployment. In a mechanical deployment method, linesor patterns of spikes protrude from a carrier surface or are extractedfrom the core of a catheter used for remote delivery. In a balloondeployment method, the spikes are mounted on an expandable balloon(similar to those used in angioplasty). In a balloon-assist method, thespikes are mounted on a carrier surface, and the carrier surface ispushed against the plaque under the expansion force of a balloon. Theballoon in this method is used as means to stabilize the spikes withinthe artery and assist in pushing the spikes into the artery wall, butnot to perform a simultaneous balloon angioplasty. Related methods areprovided for insertion of the spikes in a compressed state into theblood vessel and expanding them to the intended shape for plaquemicroperforation and serration, and then re-seating the spikes forwithdrawal. Several variations for spike mounting and delivery, andvariations for spike cross-sectional profiles and for placement in linesand other patterns are further disclosed.

Preferred embodiments include a delivery device in which spikes areformed like polymer gum drops on a carrier ribbon or strip which areattached on the surface of an expansion balloon that is folded to acompact state for delivery. Another embodiment has spikes shaped assharp pins carried on mesh bases and folded into flaps of an expansionballoon. Another embodiment of the delivery device has spikes that aredeployed from and retracted back into a mechanical carrier. Anotherembodiment of the delivery device has spikes carried or projectable fromthe surface of a catheter carrier and an external multi-lobed balloonfor pressing the spikes in circumferential sections against the plaque.Yet another embodiment has spikes carried on an accordion-likestructure. The spikes may also be carried on ribbons strips of a slittedmetal tube which are biased by shape memory outwardly toward thearterial wall. The spikes may be carried on a button structure forattachment to a carrier, or may be carried on a stretchable meshstructure over an expansion balloon. The spikes may be arranged invarious patterns on the delivery device depending on the cleavage planesdesired to be formed in the plaque.

In some embodiments an intravascular device can comprise a carrier andan expansion apparatus. The carrier can be reversibly expandable andcollapsible within a vessel and can comprise a metal sheet formed in atubular shape and can have ribbon strips extending between opposite endsof the sheet in a longitudinal direction of the carrier. The ribbonstrips can each be formed with a plurality of elongated protrusionsthereon, each of the protrusions attached to the ribbon strip at a base,a height of the protrusion defined by a distance extending from the baseto a top edge, the top edge being elongate and extending essentially ina line that defines the top most portion of the protrusion. Each ribbonstrip can be separated from adjacent ribbon strips by a single slit oneither side which is oriented in the longitudinal direction and extendsup to but not including one or both opposite ends of the tubular shapeof metal sheet. The ribbon strips can be unconnected between saidopposite ends of the tubular shape of metal sheet thereby being leftfree to expand into and form cleavage lines or planes in the plaque. Theexpansion apparatus can be used to actuate the ribbon strips each withthe plurality elongated protrusions to pierce a luminal surface of theplaque with lines or patterns of microperforations which act asserrations for forming cleavage lines or planes in the plaque.

Other objects, features, and advantages of the present invention will beexplained in the following detailed description of preferred embodimentswith reference to the accompanying drawings.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a schematic illustration of the invention method forperforation and serration treatment of atherosclerotic plaque.

FIGS. 1A-1C illustrate a preferred embodiment of a delivery device inwhich FIG. 1A shows spikes formed like polymer gum drops on a carrierribbon or strip, FIG. 1B shows attachment of the strips 16 on a balloon,and FIG. 1C shows a compact folded balloon.

FIGS. 2A-2F illustrate another preferred embodiment of the deliverydevice in which FIG. 2A shows the spike in the shape of a sharp pin,FIG. 2B shows how the pin is folded into a mesh, FIG. 2C shows the meshannealed to the outer surface of an expansion balloon, FIG. 2D shows thepin folded into the mesh and under a flap of the balloon, FIG. 2e showsthe pins deployed when the balloon is expanded, and FIG. 2F shows adetail view of the base of the pin.

FIG. 3 shows the arrays of pins in the above-described embodiment foldedwithin accordion-like flaps along the length of the expansion balloon.

FIGS. 4A and 4B illustrate another embodiment of the delivery device inwhich spikes are deployed from and retracted back into a mechanicalcarrier.

FIGS. 5A-5D illustrate other embodiments of the delivery device whichhas spikes carried or projectable from the surface of a catheter carrierand an external multi-lobed balloon for pressing the spikes incircumferential sections against the plaque.

FIGS. 6A-6C show another embodiment for the delivery device in which thespikes are carried on an accordion-like structure

FIGS. 7A-7C show three variations for mounting a spike on a carrier.

FIG. 8 illustrates an embodiment of the delivery device in which thespikes are carried on a stretchable mesh structure.

FIGS. 9A-9E illustrate various patterns for arrangement of the spikes onthe delivery device.

FIGS. 10A-10C show another embodiment for the spike carrier of thedelivery device in which the spikes are carried on ribbon strips of aslitted metal tube which are biased by shape memory outwardly toward thearterial wall.

FIGS. 11A-11C show a variation of the above-described embodiment inwhich the ribbons of the carrier sheet contain a series of holes.

FIGS. 12A-12C show another variation of the above-described embodimentin which the middle section of the carrier sheet has slitted ribbonswhich are biased outwardly toward the arterial wall.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENT

The conventional practice of compression of plaque by expansion pressureduring balloon angioplasty, i.e., by applying a high pressure expansionforce equally in all directions radially from the inside to aheterogeneous, roughly circumferential plaque-structure, can produceunpredictable and inconsistent results. In typical treatment ofatherosclerotic plaques, the angioplasty balloon is inflated with 4 to 8atmospheres of pressure, and pressures up to 22 atmospheres may berequired in some cases. Such high pressures can cause injury to theintima and media in the artery at the treatment location. Arterial wallinjury is one of the major stimulants to intimal hyperplasia, smoothmuscle cell replication and intravascular scarring causing occlusion.Plaque is heterogeneous in nature composed of varying masses of soft andhard materials, calcium and highly variable topography, and can give wayalong paths of least resistance. Therefore, when standard balloonangioplasty is performed, some of the plaque inevitably fractures. Theextent and severity of the fracture, the angiographic result and themorphology of the artery surface that result will vary significantlyfrom one patient to the next. This leads to many cases in which stentsare required to be implanted, which prolongs the surgical procedure, andincreases medical risk and costs. Moreover, the clinical evidenceindicates substantial disadvantages with using stents, including bodyrejection of a large mass of foreign material, and the emplacement ofextensive surface area of a stent that may become sites forre-accumulation of plaque and re-stenosis. There is some evidence thatstents may stimulate biological reaction that limits the long-termpatency of the procedure. Stent also cause problems with kinking of theartery in areas where the artery is significantly flexed, such as at theknee joint. Stents may also fracture and break due to material stress.

In the present invention, the plaque is treated by a perforation andserration procedure that forms lines or patterns of microperforationswhich act as serrations for forming cleavage lines or planes in theplaque. The serrations will result in more predictable and more uniformexpansion characteristics in the plaque during a subsequent balloonangioplasty, thereby helping to make the balloon angioplasty a moreconsistent and predictable process. It is expected that plaque preparedby the perforation and serration procedure can be dilated with a muchlower pressure during angioplasty, i.e., less than 4 atmospheres, and aslow as 2 atmospheres or less. The ability to perform angioplasty atlower pressures will create less plaque dissection and less arterialinjury. Less arterial injury may lead to better rates of acute successbecause there is less dissection, and may also lead to better long-termresults since there is less injury to the intima and media in the arteryat the treatment location.

The forming of serrations in the plaque through microperforation isdeemed to provide a line along which expansion energy may be released.The microperforations are formed in a pre-angioplasty procedure ofinserting a carrier carrying an array of small, sharp spikes which arepressed under a slight expansion force to pierce partway into the plaqueand without causing injury to the arterial walls. Since plaque usuallyfractures longitudinally during standard balloon angioplasty, the spikesare preferably arranged in a mostly longitudinal pattern. Othervariations include configurations with a diagonal or zig-zag patternconsistent with the expected ways that plaque commonly fractures. Theheight of the spikes is designed to pierce the plaque surface to createserrations for expansion lines, but not deep enough to cut though theplaque thickness. Materials research on crack propagation can be appliedto select the optimal configurations for spike patterning to obtain thebest characteristics in plaque compression.

Artery vessels are comprised of organized lamellar structure withrepeating structural and functional units of elastin, collagen andsmooth muscle cells. The lamellar structure is prone to split and createa cleavage between adjacent elastic lamellae. Basically, in angioplastythe expansion is partly due to the arterial stretching. In addition theplaque material has low ductility and fracture stresses can propagatenon-uniform cracks in the brittle material. In the pre-angioplastypreparation of the plaque material, the microperforations act asnucleation sites for void formation. In the subsequent application ofballoon angioplasty, stress energy for compressing the plaque isreleased along the serration created by the series of pinpoint voidsformed in the plaque to control crack propagation. If balloonangioplasty is applied without the plaque serration step, the amount ofstress energy applied can be very high prior to initiation of crackformation, and once the crack begins the energy can quickly propagatealong brittle crack areas, leading to unpredictable plaque ripping,tearing, or dissecting. The pre-angioplasty preparation of the plaquewith microperforations avoids high stress concentration at an initialpoint of fracture, and assists stress release along the series of voidsdesigned to guide the fissure event and provide more predictablecleavage lines in the plaque.

The perforation and serration procedure will promote more uniformcompression of the plaque under expansion pressure during angioplasty.The portion of the plaque that does not compress will expand better andwill be less likely to break or fracture. Forming serrations in thesurface of the plaque is expected to provide better and more uniformcompression under low pressures in angioplasty and will produce betterplaque compression characteristics than the standard approach ofapplying high expansion pressures against the full length, width, andthickness of the plaque. This is expected to result in compressing theplaque with fewer tendencies for dissection, allowing the plaque to openalong more natural lines, and therefore expanding the lumen larger andwithout causing arterial injury.

The perforation and serration procedure is expected to providesignificant advantages as compared to prior proposals for cutting orscoring the plaque with blades or sharp edges. Some prior proposals havecalled for performing balloon angioplasty with longitudinal cuttingblades affixed to the sides of the angioplasty balloon. However, whenthe balloon is expanded, the cutting blades are forced into the walls ofthe artery. Moreover, at the typical high pressures for balloonangioplasty, the cutting blades may be forced into the arterial walls athigh pressure, because all the force of the balloon is concentrated onthe projecting cutting blades. Because the cutting action of the bladeis performed at the same time as the expansion of the artery withballoon angioplasty, there is no a prior preparation of the plaquebefore balloon angioplasty and there is a risk that the artery itselfmay be cut and forced open and will expand as it is forced. The arterymay thus be injured in a traumatic manner and at high pressures. Cuttingblades or edges also have relatively long linear lengths that will cutacross non-uniform plaque material, producing uneven cuts. Even smallercutting blades will encounter at times areas of dense calcificationamong softer masses that could be fractured by the linear cutting bladesor edges. In contrast, microperforations form tiny holes at specificprick points across the plaque mass and taken together as a line orpattern of perforations result in more reliable serrations.

Other prior proposals have suggested scoring the plaque with a metalwire or tabs arranged around an angioplasty balloon in a spiral ordouble spiral manner. The outer wire or tabs may be forced into the wallof the artery when the balloon is expanded during angioplasty at highpressure. The orientation of the wire on the outside of the angioplastyballoon focuses the expanding balloon pressure on the wire. Thereforethe pressure exerted by the wire against the wall of the artery farexceeds the pressure in the balloon generating a very high localizedpressure at the working tip of the wire. The wire or tabs may cut deeplyinto the wall and may cause increased injury beyond that caused by thehigh pressure alone. In addition, because the wire is wrapped around theballoon in a spiral manner, the distance between the wire windingsaround the outside of the balloon will change at different balloondiameters. This causes some axial displacement of the wires so that itmay actually undermine artery plaque by causing it to “dig up” theplaque. This may even create dissection planes that are morecircumferentially oriented (as opposed to longitudinal) and may be morelikely to function as flow limiting dissections.

In contrast, the perforation and serration procedure can be performed atlow balloon or other expansion pressures. The microperforations areformed by small sharp spikes which can pierce into the plaque withoutdigging it up. Forming tiny prick points with the small spikes willleave most of the surface of the plaque intact, will not injure thearterial wall, and will leave most of the plaque structure intact formore predictable and better compression characteristics. The serrationsallow the plaque to be compressed at lower pressures during thefollowing angioplasty. The plaque is also less likely to formdissections, both because it can be treated at lower pressures, andbecause the plaque has expansion lines serrated in it that allow it toexpand in a more orderly manner.

Because the perforation and serration procedure forms small prick pointsin the plaque, it may also afford a very effective means of distributinganti-plaque medication into the plaque from a drug-eluting balloonduring angioplasty or from a drug-eluting stent after angioplasty. Themicroperforations may serve to retain more medication within the plaquemass, acting as a portal to the inner structure of the plaque for themedication to work. In the pre-angioplasty procedure, the spikes mayalso be used as a carrier for drug delivery by coating the spikesthemselves with drugs.

The perforation and serration procedure is thus designed as a minimallyinvasive approach for creating predictable cleavage planes inatherosclerotic plaque in preparation for balloon angioplasty. Thecleavage planes are enabled by the serrations formed by numerous smallperforations into the plaque in a predetermined pattern on the plaquesurface. By creating a preformed expansion line or line of cleavageprior to angioplasty, the artery is prepared so that it will respond toballoon dilatation in a more predictable manner with less likelihood ofdissection or elevated surface flaps. The need for stent placement tosmooth the artery surface and retain plaque dissections or flaps canthus be significantly decreased.

A suitable device for performing the perforation and serration proceduremay be designed in a number of ways, as described below for thefollowing preferred embodiments which are illustrative of the principlesof the present invention. Three different methods for spike deployment,through mechanical, balloon, and balloon-assist deployment, aredescribed with respect to certain preferred delivery designs. Thelocations, length, and configuration of the spikes may be designed forvarying types of lesions and arterial sites being treated. For example,heavily calcified lesions may require that the spikes be more closelyspaced and penetrate a little deeper into the plaque. Some devicedesigns may only be partially covered with spikes so that the hardestpart of the plaque is left alone and serrations are created along asofter portion of the plaque surface. Lesions that are morelongitudinally oriented may require spike placements that are fartherapart and arranged in a gradual twirling configuration.

FIG. 1 shows a schematic illustration of the invention method forperforation and serration treatment of plaque 10 at a site in an artery11 with a delivery device 12 for serration and dilatation of the plaque.The lumen L is the flow opening in the artery that has been occluded byplaque 10. The device 12 has one or more arrays 12 a, 12 b, and 12 c ofsmall, sharp spikes carried on carrier strips of surfaces which areseated on the outer surface of an expansion balloon 14 or otherexpansion device. The spikes are mounted on the carrier strips at spacedintervals and extend typically a distance 0.05 mm to 1.0 mm beyond thecarrier surface for piercing into the plaque and formingmicroperforations across the surface of the plaque. The delivery device12 may be carried in a catheter and positioned at the plaque site byinsertion into the artery through a surgical incision (not shown) andmanipulated into position by a wire 13 to the location of the plaque.The spikes and expansion balloon are initially in a deflated orcollapsed state to allow threading of the device 12 through the artery.

When the delivery device is in position, and a catheter shield (if used)is retracted, the expansion balloon is inflated through an inlet tube 13at low gas or fluid pressures to gently push the spike arrays againstthe plaque 10. Gas or fluid pressures in the range of 1 to 4 atm may beused for the pre-angioplasty procedure. The spikes create series ofmicroperforations which act as serrations along the horizontal length ofthe plaque. The serrations allow cleavage lines or planes to be formedin the plaque at these locations under compression forces during afollowing angioplasty procedure. As the spikes are pressed into theplaque, the plaque is also compressed gently for a given measure ofdilatation. When the serration has been performed, the balloon isdeflated by suction of fluid or gas out through the tube, such that thedelivery device 12 can resume its collapsed state so that it can bewithdrawn from the artery.

A standard angioplasty balloon may thereafter be used to compress theplaque against the artery walls to open the lumen. The compression ofthe plaque during angioplasty can take place evenly and with minimaldissection or cracking along the cleavage lines formed by themicroperforations. Due to the pre-angioplasty preparation of the plaque,the balloon angioplasty can be performed at low pressures of less than 4atmospheres, and as low as 2 atmospheres of pressure or less. If thepre-angioplasty procedure has compressed the plaque sufficiently, it maynot be necessary to follow it with a standard angioplasty.

FIG. 1A illustrates a preferred embodiment of the delivery device inwhich the spikes are formed like polymer gum drops 15 on a narrow ribbon16. The polymer is heated and fed in liquid form to an ejector thatejects a drop in position on the ribbon. The drop rapidly cools as it isejected, and forms an inverted cone shape that comes to a hard sharppoint by tapering off the fluid from the ejector. The potential shape ofthe spike can include other types of pointed shapes, such as a long,pyramidal shape, a tri angle shape, an arrow shape (longer and sharp inone axis and narrow and dull in the perpendicular axis), a gum dropshape, a narrow rectangle shape, a pin shape, a needle shape, andothers. Other materials could be used to form the spike, including apliable metal, such as Nitinol, or carbon nanotubes.

After hardening and processing of the polymer, the narrow strip 16 isannealed to the surface of an expansion balloon or other mechanicallyexpansive carrier. The strips may also be interwoven into a mesh(polymer, metallic, or fabric). The strips or mesh are arranged in apattern that envelopes the surface of the expansion balloon or othermechanically expansive structure. FIG. 1B shows attachment of the strips16 (end view) along the longitudinal length of a balloon 17 at a number(8) of circumferential positions. The balloon may be folded at folds 18to bring the sharp points 15 on four adjacent strips to nest with thoseof the other strip, and then the two lobes of the balloon are foldedover again to bring the sharp points of the other four adjacent stripsinto nested configuration. FIG. 1C illustrates the resulting, compactfolded balloon in which all the sharp points are folded within to avoidengaging the plaque material when the device is being moved intoposition.

FIG. 2A illustrates another preferred embodiment in which the spike isin the shape of a sharp pin 21 that has a lower end bonded to a mesh 22that is annealed to the surface of the expansion balloon. The lower endof the pin 21 is held by the polymer mesh so that the spike stands erect011 the surface of the balloon when the balloon is inflated. The pin 21may be constructed of polymer, metal composite, silicon or carboncomposite or carbon nanotubes (single or multi wall).

FIG. 2B illustrates how the pin 21 is folded by pressing it into themesh 22. In FIG. 2C, the mesh 22 is shown annealed to the outer surfaceof the expansion balloon 23. In FIG. 2D, the pin 21 is laid downlaterally and perpendicularly to the axis of the balloon-center line forplacement, so that the pin is folded into the mesh and under a flap ofthe balloon. The entire mesh in the depressed mode is nearly swallowedup by the balloon material. With the pin laid down flat within the mesh,the balloon is protected from puncture of the balloon surface. The flapon the balloon unfolds during balloon expansion, and the meshes areunfolded so that the pins are quickly popped out straight and erect.

FIG. 2E shows the pins 21 deployed and standing erect on the expansionballoon 23 after the catheter shield 24 is withdrawn and the balloon isinflated. The pins are exposed and stand erect on the mesh sheets 22that are mounted on the balloon surface. The pins stick out peripherallyand can pierce into the plaque as the balloon is further inflated. FIG.2F shows a detail of the base of the pin 21 entwined in the mesh weavingto center the lower end of the pin on the mesh 22 and hold the pin erectwhen the mesh is unfolded and the balloon is expanded.

In FIG. 3, arrays of pins 21 are shown folded within accordion-likeflaps of a pre-angioplasty expansion balloon 23 of the device which arefolded in alignment with a longitudinal axis LG of the balloon. In thisdesign, half the flaps and pins are folded toward one end of theballoon, and the other half are folded toward the other end of theballoon. When the balloon is expanded, the mesh strips will reorientwith respect to the surface of the balloon and face outward toward theplaque on the artery walls. The flaps of balloon material betweenparallel rows of spikes can be made extra flexible and pliable and maybe formed as a folding crease. When gas or fluid pressure is injected inthe balloon, the flaps are the first areas to pop out and help to pointthe spikes outwardly toward the plaque.

FIGS. 4A and 4B illustrate another embodiment of the delivery device inwhich an expansion balloon is not used but rather the spikes 41 aredeployed from and retracted back into a mechanical carrier 40. Thecarrier has a plurality of tunnels 42 a in its interior each of whichholds a spike in a ready position within and has a spike exit hole 42 bwith its axis oriented radially to the outer surface of the carrier.When the carrier 40 is in position at a plaque site, the spikes aremechanically or hydraulically actuated, such as by a gas or fluidpressure force indicated by arrows 43, to travel through the tunnels andproject radially from the spike exit holes 42 b. The spikes have sharppoints at their tips for creating microperforations in the plaque, butare flexible in their shafts so that they can be deployed from a layingdown position and turned to a 90 degree standing up position. In thatposition, the spikes are pointed toward the wall of the artery and theplaque. As an alternative for mechanical actuation, the spikes may beactuated by respective levers which are pulled or pushed by a cable.Other types of mechanisms similarly may be used for mechanicallydeploying the spikes from the carrier.

FIGS. 5A-5D illustrate other embodiments of the delivery device forpre-angioplasty serration and dilatation. In the embodiment shown inFIG. 5A, rows of spikes 51 are bonded to a ribbon, rod, tri angle orother shaped carrier 50. An outer balloon 52 is divided into quadrantsand shaped with cutout areas that conform to spaces in between thespikes. The balloon 52 is inflatable in quadrants circumferentiallyaround the carrier 50. As one quadrant of the balloon 52 is inflated,the spikes on the opposing side of the carrier 50 are pressed into theplaque on the artery wall. The balloon 52 on the side of the onequadrant is deflated, then the next quadrant is inflated to press thespikes on another opposing side into a next section of the plaque. Thisis repeated for the other quadrants as needed until the spikes on allsides have been pricked into the circumference of the plaque surface.

In FIG. 5B, another embodiment of the delivery device has rows orribbons of spikes 53 bonded to an internal carrier balloon 54 sleevedinside of a tube 55 which has spike holes 55 a aligned with thepositions of the spikes spacing found on the internal carrier balloon54. An outer balloon 56 is shaped with cutout areas that conform to thespaces between the spike holes. The outer balloon is able to be filledin quadrants circumferentially around the carrier device. As onequadrant expands, the tube is pressed on its opposing side against theplaque. The internal carrier balloon 54 is inflated and the spikes arepressed out of the holes and pierce into the plaque on the side incontact with the plaque. This is repeated for the remaining quadrantsuntil the spikes have been pricked into the circumference of the plaquesurface.

In the above-described embodiments, the multi-lobed segments of theexpanding balloon stabilize and support the spikes as they enter theplaque to cause perforation. The spikes may be constructed of anysuitable material, such as polymer, pliable metal, or carbon nanotubes,and may have one of many possible shapes, including a pin shape, aneedle shape, a long, pyramidal shape, a triangle shape, an arrow shape,a gum drop shape, a narrow rectangle shape, and others. The balloon, asit is expanded, is also used to compress the plaque to a certain degreeand dilate the lumen of the artery. The balloon may be manufactured tobe inflated with CO2 or with liquid.

FIG. 5C shows another embodiment where rows of spikes 57 are bonded toor etched out of a ribbon, rod, triangle or other shaped carrier 58. Anouter balloon 59 is multi-lobed capable of being inflated in sectionsand conforming to spaces in between the spikes. FIG. 5D shows a furtherembodiment in which the spikes 57 are seated on an inner balloon in adelivery catheter 58. The catheter walls have holes 58 a located toallow the spikes to poke through when the inner balloon is inflated. Onthe outside of the catheter in this embodiment is multi-lobed externalballoon 59 which is inflatable in sections. As one section is inflated,the catheter wall on the opposite side is pushed against the plaque onthe arterial wall, and when the inner balloon is inflated, the spikes 57are pressed out to pierce into the plaque mass. This procedure isrepeated in sections circumferentially around the catheter until allareas of the plaque have been pierced by the spikes.

FIGS. 6A-6C show another embodiment for the delivery device in which thespikes (welded, bonded, or shaped out-of-plane) are married at joints onthe circumference of an accordion-like structure provide for amechanical expansion engagement with the plaque. In the pre-loadeddelivery position shown in FIG. 6A, the accordion-like structure 60 isstretched longitudinally over the surface of the delivery catheter 61,and the spikes 62 lay flat against the catheter sheath. This position ofthe spike structure is used when the catheter is inserted and withdrawn.Once the spike structure is in position at the plaque site, theaccordion-like structure 60 has its opposite ends moved together, suchthat the spikes 62 are pressed out radially to pierce the plaque, asshown in FIG. 6B. The compression of the accordion-like structure 60 maybe actuated by mechanical pulley, polymer fiber or wire attached atpoints A disposed symmetrically around the circumference of thecatheter. The wires are pulled uniformly at one end of theaccordion-like structure to compress lattice segments of the structureand decrease the distance between the spike connector joints, therebyforcing the spikes outwardly toward the lumen wall. In FIG. 6C, theaccordion-like structure is shown laid out in plan view and elevationview, and pre-loaded in end view.

FIGS. 7A-7C show three variations for mounting a spike on a carrier. InFIG. 7A, the spike 70 (pyramid point) is mounted on a button 71 havinglower shanks 71 a for seating on a carrier. In FIG. 7B, the spike 72(pin) is mounted on a button 73 having button holes 73 a for attachmentby fasteners to the carrier. In FIG. 7C, the spikes 74 (sharp tips) aremounted on a button 75 having holes 75 a for fastening to the carrier.The buttons may be entwined within a fabric, woven pattern or bagstructure using the button holes or mounting shanks on the buttons.These spike-mounting buttons may be used with any of the above-describedembodiments for the delivery device.

FIG. 8 shows an embodiment in which the spikes are carried on astretchable mesh structure 80 surrounding an expansion balloon which isinflated to stretch the mesh outwardly on all sides and push the spikesinto the surrounding plaque mass. The spikes may be interwoven into themesh structure. When the balloon is deflated, the mesh snaps back withthe collapsed surface of the expansion balloon.

In all the embodiments described above, the spikes may be made frommetal, polymer, silicon or carbon composite (with or without an inertcoating), a super-elastic material, or carbon nanotubes. The spikes mayhave a preferred height (from base to tip) of 0.05 mm to 1.0 mm. Thespike tip may be needle-like with a needle head [or mounting. As analternative, the tip can be shaped with a thin tubular cross-section (asin a needle for transporting fluid through it), or a groove or slothaving one dimension that is much larger than the other where the largerdimension of the groove is less than 2 mm and the smaller dimension ismuch less than the first, and a point where the overall head radius issmall less than 0.4 mm (as in a pin head), or a collection of very smallpoints where the overall head radius is less than 0.05 mm (as in carbonnanotubes). It may instead be formed by carbon nanotubes presenting acollection of very small points to form a sharp tip. The spikes may alsobe coated with, or provide transport for, plaque-inhibiting medicationfor deposition into the plaque site. In the preferred embodimentsdescribed above, the spikes may be mounted on the surface of a balloon,or on a catheter, or may be mounted on a mechanically actuated surface.

The spikes may have various shapes, may be made from a variety ofmaterials, may be deployed in different ways, and may be attached to thedelivery device using different methods. The spikes are arrayed in anydesired pattern to create a cut-along-the-dotted-line serration in theplaque mass so that it can become a cleavage plane or expansion planeduring dilatation by balloon angioplasty.

The configuration of the spikes may be oriented in different mannersdepending upon the arterial disease and the plaque formation requiringtreatment. The spikes may also have through-holes or inner channels foreluting medication through the spike to the surface of the plaque.

FIGS. 9A-9E illustrate various patterns for arrangement of the spikes onthe delivery device, i.e., circumferential, partial circumferential,patch, spiral/diagonal, and longitudinal. The configurations aredesigned for different functional purposes in managing atheroscleroticplaque or in ease of manufacture or ease of use. Plaque with certaincharacteristics, such as very heavy calcification, may be treated withspikes that are configured in more of a circumferential or diagonalpattern, crossing the line of blood flow, since this morphology ofplaque tends to form clusters or mounds of calcium. The spikes that maynot be able to perforate this type of plaque or portions of this type ofplaque very readily, but may be able to cut around the areas of worsedisease and permit the inner circumference of the whole artery toexpand. The spikes are arranged generally longitudinally, consistentwith the fracture characteristics of plaque in most situations and withmost plaque morphologies, and may be configured in a straight line. Thestraight, longitudinal lines of spikes may be very short, consisting offive spikes or less and may be quite long, consisting of 100 spikes ormore. The longitudinal lines of spikes may be very dose together, withas many as 20 lines distributed on the circumference of the arteryluminal surface, or there may be as few as a single line of barbs orspikes. The lines of spikes may also be in a slight diagonal or in azig-zag fashion. The configuration of the barbs or spikes is determinedin accordance with the best expected mechanism for post-angioplastyplaque dissection. They are designed to create cleavage planes orexpansion lines suitable for the expected composition of the plaque andthe pressures expected to be exerted upon it. The orientation and depthof desired cleavage planes may vary significantly with the parametersfor balloon angioplasty. The spikes may also be constructed so that theymay provide delivery of medications. A cooperative structure such as adouble-walled balloon for pressure infusion of a small amount ofmedication agent into the plaque wall or other functionality may also beincluded.

FIGS. 10A-10C show another embodiment for the spike carrier of thedelivery device. In FIG. 10A, the spikes are carried on ribbon strips ofa slitted metal sheet which has opposite ends that are joined by eitherwelding into a tube or the strips are cut out of a tube leaving one endintact. The spikes may have various profiles, such as where the lengthof the spike base or head is equal to the width of the ribbon strip, orthe spike base length is a fraction of the ribbon width and is centeredat the middle of the ribbon strip, or where the spike base is a fractionof the ribbon width and positioned at varying locations across theribbon width or may have multiple spikes at any given ribbon section ofwidth. FIG. 10B is an elevation view of the sheet. FIG. 10C shows thesheet after heat treatment to provide a shape memory in which theribbons are spring-biased radially outward toward the arterial wall forgenerating perforations in the plaque. The shape memory may be usedalone for mechanical engagement of the spikes, or may be combined withan expansion balloon to allow greater control of forces to be applied.

FIGS. 11A-11C show a variation of the above-described embodiment inwhich the ribbons of the carrier sheet contain a series of holes. Theholes serve as points for attachment of strings, cables, or wireelements, configured in such a way, that when pulled can provideadditional “Support and force outward against the lumen wall. FIG. 11Bis an elevation view of the sheet. FIG. 11C shows the sheet after heattreatment to provide a shape memory for spring-biasing the ribbonsradially outward. The shape memory may be combined with an expansionballoon to allow greater control of forces to be applied.

FIGS. 12A-12C show another variation of the above-described embodimentin which both longitudinal ends of the tube are kept intact, leavingonly the middle region with slitted ribbons. One end contains a seriesof holes which serve as points for attachment of strings or wireelements that when pulled can provide additional support and forceoutward against the lumen wall. FIG. 12B is an elevation view of thesheet. FIG. 12C shows the sheet after heat treatment to provide a shapememory for spring-biasing the middle section of ribbons radiallyoutward.

A general procedure for the pre-angioplasty perforation and serration ofa plaque site will now be described. A delivery catheter is constructedfor the purpose of plaque perforation in an endovascular environment. Aguidewire is threaded along an artery from a percutaneous access site ora surgical incision to a lesion intended for treatment. A catheter ispassed over the guidewire with an end of its sheath maintained gas-tightand fluid-tight for operational control externally by an operator. Oncethe catheter is in position at the lesion site, a spike delivery deviceis advanced down the hollow, tubular shaft of the sheath over theguidewire. The delivery device for the typical perforation-serrationcatheter is intended to be as large as 8 Fr and more likely 5 Fr or lessin diameter. The guidewire lumen maybe 0.014 inches or up to 0.035inches in diameter. The length of the delivery catheter may be as shortas 40 cm but more likely 75 to 80 cm for a short length and 120 to 135cm for a long length. The catheter has another tubular channel forinflating or actuating the expansion balloon or apparatus on thedelivery end of the catheter.

When the expansion balloon, mechanical expansion apparatus or otherapparatus is actuated, the spikes on the delivery device are pressedtoward the plaque. The spikes are driven into the plaque and createmultiple perforations forming intended serrations in the surface of theplaque in a proscribed pattern. The expansion balloon or apparatus issomewhat compliant and may be inflated further to compress the plaqueand enlarge further. When the desired perforation of the plaque has beenachieved, the expansion balloon or apparatus is de-actuated, disengagingthe spikes from the plaque, and once collapsed is withdrawn through thecatheter sheath.

After the preparation procedure for the plaque, the plaque can becompressed and the artery lumen safely and accurately dilated andstretched during standard balloon angioplasty to its intended diameterwithout creating numerous and substantial dissections and elevatedflaps. The perforation and serration enable the plaque to be dilatedmore evenly and smoothly and avoid forming random cracks that may leadto dissection, arterial injury, and residual stenosis. The plaque, afterit has been pre-treated with perforation and serration, may also bedilated with lower pressure (usually 2 atmospheres or less) than thatwhich is used in standard balloon angioplasty. The lower intra-balloonpressure causes less injury to the artery wall. This “low pressure” or“minimal injury” angioplasty is less likely to cause the biologicalreaction that often follows balloon angioplasty with neointimalhyperplasia or smooth muscle cell replication.

In addition, the plaque is likely to expand with less fracturing ordissection during balloon angioplasty. This decreases the need for stentplacement to be used to treat dissection or residual stenosis afterballoon angioplasty. If extensive dissections and non-smooth luminalwall surfaces require a stent to be placed, the improved dilatation ofthe lumen obtained with pre-angioplasty perforation and serration wouldallow a stent to be more fully opened.

In cases where one or more local sites of post-angioplasty dissectionsor flaps present themselves, a thin, ring-shaped tack device may beplaced at only the location of each specific problem site, so that theamount of foreign material emplaced as a retaining structure for plaquein the blood vessel can be minimized and exert only low lateralpressures against the post-angioplasty surface. A novel method anddevice for applying a ring-shaped tack device as a retaining structurefor plaque in the blood vessel is described in U.S. patent applicationSer. No. 11/955,331, filed Dec. 12, 2007, entitled “Device for TackingPlaque to Blood Vessel Wall”, which is incorporated by reference herein.The described procedure for perforation and serration of the plaqueperformed with a given amount of arterial dilatation may be sufficientto obtain compression of the plaque sufficiently that no balloonangioplasty or stent emplacement is required. Only one or a few of thering-shaped tacks may be needed to secure the .compressed plaque to theartery wall, thereby obtaining the desired medical treatment withminimal forces being applied to the arterial walls and with a minimum offoreign material emplaced in the body. The present invention istherefore deemed to include the alternative of combining the perforationand serration procedure with the procedure for applying localized tacksat specific locations for plaque retention.

It is to be understood that many modifications and variations may bedevised given the above described principles of the invention. It isintended that all such modifications and variations be considered aswithin the spirit and scope of this invention, as defined in thefollowing claims.

What is claimed is:
 1. A method of treating an atherosclerotic vessel ata treatment site in a wall of the vessel, comprising: treating a site ina vessel by expanding a balloon at a pressure of less than 4 atmospheresat the site to create a plurality of microperforations in the wall ofthe vessel, the balloon comprising a plurality of strips, each strip ofthe plurality of strips including a plurality of microperforators spacedapart along a surface of each strip, each strip extending longitudinallyalong an outer surface of the balloon, wherein expanding the balloon ata pressure of less than 4 atmospheres forms cleavage lines or planes inan atherosclerotic plaque of the vessel wall, wherein the pressure ofless than 4 atmospheres forms microperforations while leaving most ofthe surface of the atherosclerotic plaque intact, leading to lessseparation of the atherosclerotic plaque from the vessel wall, whereinthe microperforators each comprise a tip comprising a first dimensionand a second dimension, wherein the first dimension is greater than thesecond dimension; and removing the balloon from the site.
 2. The methodof claim 1, wherein the plurality of microperforators spaced apart alonga surface of each strip are spaced equally apart.
 3. The method of claim1, wherein the plurality of microperforators along each strip all have asame length.
 4. The method of claim 1, wherein expanding the balloon isperformed at a pressure of less than 2 atmospheres.
 5. The method ofclaim 1, wherein the plurality of microperforators comprise arectangular shape.
 6. The method of claim 1, wherein the plurality ofmicroperforators comprise a pyramidal shape.
 7. The method of claim 1,further comprising a subsequent balloon angioplasty for plaqueexpansion.
 8. The method of claim 1, wherein the plaque is dilated withlower pressure than that which is used in standard balloon angioplasty.9. The method of claim 1, wherein the cleavage lines or planes result inuniform expansion characteristics in the atherosclerotic plaque.
 10. Amethod of treating an atherosclerotic vessel at a treatment site in awall of the vessel, comprising: treating a site in a vessel by expandinga balloon at the site to create a plurality of microperforations in thewall of the vessel, the balloon comprising a plurality of strips, eachstrip of the plurality of strips including a plurality ofmicroperforators spaced apart along a surface of each strip, wherein themicroperforators are arranged only axially in the vessel, notperpendicular or diagonal to the axial direction, wherein themicroperforators have a height to pierce partway into an atheroscleroticplaque while leaving most of the plaque surface intact, each stripextending longitudinally along an outer surface of the balloon, whereinexpanding the balloon under an expansion force comprises formingcleavage lines or planes in the atherosclerotic plaque of the vesselwall without separating the atherosclerotic plaque from the vessel wall;and removing the balloon from the site.
 11. The method of claim 10,wherein the cleavage planes prevent the lifting of a flap of theatherosclerotic plaque.
 12. The method of claim 10, wherein the cleavageplanes create controlled plaque disruption.
 13. The method of claim 10,wherein expanding the balloon is performed at a pressure of less than 4atmospheres.
 14. The method of claim 10, wherein the plurality ofmicroperforators comprise a narrow rectangle shape.
 15. The method ofclaim 10, wherein top edges of the microperforators are elongate andextend essentially in a line that defines the top most portion of themicroperforators.
 16. The method of claim 10, wherein the plurality ofmicroperforations result in uniform expansion characteristics in theatherosclerotic plaque.
 17. A method of treating an atheroscleroticvessel at a treatment site in a wall of the vessel, comprising: treatinga site in a vessel by expanding a balloon at the site to create aplurality of microperforations in the wall of the vessel, the ballooncomprising a plurality of strips, each strip of the plurality of stripsincluding a plurality of microperforators spaced apart along a surfaceof each strip, each microperforator comprising a tip, each stripextending longitudinally along an outer surface of the balloon, furthercomprising an outer balloon extending over the strips, the outer ballooncomprising cutout areas that conform to the spaces in between themicroperforators such that the outer balloon does not extend over thetips of the microperforators, wherein expanding the balloon at apressure that pushes the microperforators against an atheroscleroticplaque to form cleavage lines or planes in the atherosclerotic plaque ofthe vessel wall without separating the atherosclerotic plaque from thevessel wall; and removing the balloon from the site.
 18. The method ofclaim 17, wherein the atherosclerotic plaque expands along serratedlines in an orderly, predictable manner.
 19. The method of claim 17,wherein the atherosclerotic plaque expands along serrated lines withuniform expansion characteristics.
 20. The method of claim 17, whereinthe first dimension of the tip and the second dimension of the tip forma narrow rectangle shape.
 21. The method of claim 17, wherein expandingthe balloon is performed at a pressure of less than 4 atmospheres. 22.The method of claim 17, wherein tips of the microperforators extend in aline.
 23. The method of claim 17, further comprising a subsequentballoon angioplasty.